JPH0230262B2 - - Google Patents

Abstract

A cement for fixing a bone prosthesis, the cement containing: (a) a solid phase comprising firstly polymethylmethacrylate and a copolymer of methyl methacrylate with an acrylate or a methacrylate of another alcohol, both in powder form, and secondly an organic peroxide suitable for generating free radicals; and (b) a liquid phase comprising methyl methacrylate and an accelerator for accelerating decomposition of the organic peroxide. The copolymer is an oligomer, and the liquid phase includes as the accelerator for accelerating decomposition of said organic peroxide an acrylate or a methacrylate carrying a tertiary amine function, and as a cross-linking agent a compound having at least two functions in its molecule suitable for reacting with the reactive functions carried by the polymers of the solid phase, or else a double bond and a function suitable for reacting with the reactive functions carried by the polymers of the solid phase.

Description

[Detailed description of the invention]

The present invention relates to a cement for fixing endoprosthetic devices for bones, particularly endoprosthetic devices for joints. The cement comprises: (a) a powder of polymethyl methacrylate and a powder of a copolymer of methacrylic or acrylic esters of methyl methacrylate and other alcohols; and (b) a liquid phase containing methyl methacrylate and a decomposition accelerator for the organic peroxide. This type of cement has already been covered by the British patent GB-A-No.
It is described in the specification of No. 1130653. These prior art cements, however, undergo highly exothermic polymerization reactions such that temperatures reach approximately 90° C. during solidification after placement in bone. Such temperature increases alter the surrounding bone structure and thus have a detrimental effect on the stability of the placed prosthetic device. These cements also contain tertiary amines or aromatic sulfinic acids as decomposition accelerators for the organic peroxide, but these substances exhibit obvious toxicity to living organisms. The object of the present invention is that the polymerization reaction is less exothermic, the temperature during coagulation is maintained at 56 °C below the protein coagulation temperature, and the organic peroxide decomposition accelerator is used after the final hardening of the cement. The object of the present invention is to provide a bone prosthesis fixing cement that cannot migrate into living organisms and therefore does not have any serious toxic effects even in the long term. In the cement of the present invention, in the solid phase, the copolymer is an oligomer, the alcohol is an aliphatic alcohol carrying a functional group that can later react with molecules in the liquid phase, and the liquid phase contains a number of cement molecules. a tertiary amine functional group-supported methacrylic ester or acrylic ester that solidifies in minutes as a decomposition accelerator for the organic peroxide;
A compound having at least two functional groups in its molecule that can react with the functional group of the alcohol, or a compound that has at least two functional groups that can react with the functional group of the alcohol to generate a multifunctional polymer that acts as a crosslinking agent. Compounds containing heavy bonds in their molecules are used as slow and non-exothermal cross-linking agents.
linking agent). The cement of the present invention further preferably has at least one of the following characteristics. - The oligomer is an oligomer of methyl methacrylate and oxirane group-supported methacrylic acid, such as an oligomer of methyl methacrylate and glycidyl methacrylate. - The organic peroxide decomposition accelerator that solidifies cement into lumps (or bulk) in a few minutes has the structural formula: is methylanilylglycidyl methacrylate. - Contains about 3 parts by weight of solid phase per 1 part by weight of liquid phase. A non-limiting specific example of the cement composition of the present invention is shown below. Composition of solid phase: Polymethyl methacrylate powder 24g Copolymer powder of methyl methacrylate and glycidyl methacrylate (average molar mass 1000-5000
g/mol oligomer) 12 g Benzoyl peroxide 0.3 g 36.3 g Liquid phase composition: Methyl methacrylate 10.9 g Methacrylic acid (non-exothermic slow crosslinking agent) 1.03 g Methylanilylglycidyl methacrylate 0.8 g 12.73 g Solid phase/liquid The phase weight ratio is approximately 3. The mass Z of methacrylic acid as a non-pyrogenic slow crosslinking agent is determined based on the following general formula. where m is the mass of the copolymer (in this case a copolymer of methyl methacrylate and glycicyl methacrylate), is the average functionality of said copolymer (i.e. the average number of reactive groups per copolymer chain), is the average molar mass of said copolymer, M′ is the molar mass of the reactant molecule introduced into the liquid phase (methacrylic acid in this case), already 86 g/mol, f′ is the functionality of said reactant molecule (in this case for,
f′=1). The mass of benzoyl peroxide and the mass of methylanilylglycidyl methacrylate are adjusted to obtain the desired curing time. The polymerization reaction time is about 12 minutes. Fillers such as X-ray opacifiers (in particular zirconium dioxide) may be added to the solid phase, and other monomers (eg butyl methacrylate or isobutyl methacrylate) and stabilizers may be added to the liquid phase. The hardening of the cement into a mass occurs through two successive steps corresponding to two different reactions after mixing the liquid and solid phases. Despite the high proportion of solid phase, the viscosity of the mixture before hardening into a mass is below that of known cements. The first step is short and involves rapid curing into a mass and fixation of the prosthetic device;
The steps involve strengthening the cement over a longer period of time. (1) Radical Polymerization Step Hardening into a mass first occurs by radical polymerization of the acrylic acid monomers present, namely methyl methacrylate, methacrylic acid and methylanilylglycidyl methacrylate. The free radicals that initiate this polymerization reaction are generated by the reaction of benzoyl peroxide with methylanilylglycidyl methacrylate. These free radicals cause the radical polymerization reactions of methyl methacrylate and methacrylic acid to occur slowly, but they do not affect the polymer chains forming molecules with double bonds, that is, methylanilylglycidyl methacrylate molecules. It also performs the function of introducing. Therefore, methylanilylglycidyl methacrylate plays the role of a primer, that is, a decomposition accelerator for benzoyl peroxide, and the role of a monomer. The polymer chain growth reaction is then promoted by partial dissolution of the polymethyl methacrylate powder and partial dissolution of the copolymer powder of methyl methacrylate and glycidyl methacrylate. Such a hardening accelerating effect (gel effect) due to an increase in viscosity is also seen in known cements.
The polymerization reaction increases in rate and, since double bond cleavage is an exothermic reaction, a considerable amount of heat is released. In known cements, a portion of the radiated heat is absorbed by the polymethyl methacrylate powder. In addition to this powder, the cement according to the invention contains considerable amounts of copolymers, which also absorb a portion of the released heat. Oligomer (methyl methacrylate-glycidyl methacrylate) has a small molar mass, so
The proportion of liquid methyl methacrylate can be reduced (without changing the viscosity) and thus the rate of heat release can be reduced. A mixture containing dimethyl-para-toluidine as a polymerization reaction catalyst instead of methylanilylglycidyl methacrylate, but not containing a copolymer of methyl methacrylate and glycidyl methacrylate, and a mixture as described above have a calorific value under the same conditions. As a result of the measurement test,
The maximum temperature was 80°C to 90°C in the former case and 55°C in the latter case. 55°C is lower than the coagulation temperature of proteins (56°C) and therefore there is much less risk of degenerating bone tissue in the vicinity of the cement placement zone. Instead of relatively toxic tertiary amines, such as dimethyl-para-toludine, we use compounds that also act as accelerators, but also form copolymers with the main monomer, thereby reducing the long-term toxicity caused by these molecules. becomes extremely low. (2) Formation of a three-dimensional network structure At the end of the radical polymerization reaction, the cement has already hardened, but this cement contains chains carrying reactive functional groups that form a three-dimensional network structure. The rate of formation of such a network is slower than the rate of polymerization of radical steps. At this rate, approximately one week is required for the structure to stabilize. In this case, the cement medium contains the chains formed by the radical polymerization reaction in the first step,
There are oligomeric chains of random copolymers of methyl methacrylate and glycidyl methacrylate provided in the solid phase. The former chain has the formula: , with several carboxyl functional groups randomly distributed along the chain. The structural units of these chains mainly include methyl methacrylate units, some methylanilylglycidyl methacrylate units, and some methacrylic acid units. The latter chain can be represented by the formula: The carboxylic acid and oxirane functional groups react within the bulk of the cement to cleave the oxirane ring and form a hydroxyl. In this way two separate chains are covalently linked to each other. The formation of this type of network proceeds within the bulk of the cement, and after about a week it becomes a fully-fledged crosslinked network, which strengthens the cement and inhibits creep. The cement will ultimately have a network structure with half-inserted linear chains of polymethyl methacrylate. The cement thus formed exhibits mechanical properties as good as known cements,
Miscibility is equally good despite the high proportion of solid phase. Moreover, this cement is different from known ones,
It does not exhibit excessive heat generation during curing or toxicity due to organic peroxide decomposition accelerators. If the cement of the invention is to be placed in an artificial prosthetic device, for example, the solid and liquid phases may be mixed for 2 to 3 minutes, this mixture is allowed to stand for 5 to 6 minutes, and after about 7 to 8 minutes, the cement can be placed manually or with a syringe. is used to introduce it into the bone. Although the cement composition described above is believed to be the preferred formulation for practicing the invention, some of the components of this composition may be replaced with other equally acting components, or the cement composition may be modified as required by the cement. proportion of ingredients, depending on the time to obtain adaptability.
In particular, the proportions of peroxide and methylanilylglycidyl methacrylate may be varied to some extent. Other oligomer/reactive molecule (non-pyrogenic slow crosslinking agents) combinations can also be used in the formulation of the cement of the present invention, such as those described below.

【table】

[Table] Two or more primary amines in each molecule that do not inhibit
or a primary or secondary multi-amino acid containing a secondary amine functionality.
hmm

The density of the network may be varied by varying the proportion of glycidyl methacrylate in the methyl methacrylate-glycidyl methacrylate copolymer. A third monomer unit that lowers the glass transition temperature of the copolymer, such as ethyl acrylate, butyl acrylate, ethyl acrylate-2
It is also possible to change the flexibility of the copolymer by introducing diglycidyl ethers of -hexyl, n-butyl methacrylate, isobutyl methacrylate, glycidyl methacrylate, acrylic acid, methacrylic acid or bisphenol A.

Claims (1)

[Scope of Claims] 1. A cement for fixing bone prosthesis devices, especially endoprosthesis devices for joints, which comprises: (a) powder of polymethyl methacrylate and methacrylic acid of methyl methacrylate and other alcohols; (b) a liquid comprising methyl methacrylate and a decomposition promoter for the organic peroxide; phase, in the solid phase the copolymer is an oligomer, the alcohol is an aliphatic alcohol carrying a functional group that can later react with molecules of the liquid phase, and the liquid phase separates the cement for several minutes. a tertiary amine functional group-supported methacrylic ester or acrylic ester that is coagulated into a lump as a decomposition accelerator for the organic peroxide;
A compound having at least two functional groups in its molecule that can react with the functional group of the alcohol, or a compound that has a functional group that can react with the functional group of the alcohol to generate a polyfunctional polymer that acts as a crosslinking agent. A cement characterized in that it contains a compound containing a bond in its molecule as a non-pyrogenic slow crosslinking agent. 2. The cement according to claim 1, wherein the oligomer is an oligomer of methyl methacrylate and methacrylic ester carrying an oxirane functional group. 3. The cement according to claim 2, wherein the oligomer is an oligomer of methyl methacrylate and glycidyl methacrylate. 4 The organic peroxide decomposition accelerator that solidifies cement into a lump in a few minutes has the structural formula: Claims 1 to 3 are methylanilylglycidyl methacrylate.
Cement as described in any one of paragraphs. 5. The cement according to any one of claims 1 to 4, comprising about 3 parts by weight of solid phase per 1 part by weight of liquid phase.